Shauni Loopmans, Guillaume Tournaire, Ingrid Stockmans, Steve Stegen, Geert Carmeliet

Hypoxia rewires glucose and glutamine metabolism in different sources of skeletal stem and progenitor cells similarly, except for pyruvate

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism
Save to CiteDrive Show PDF

Abstract Skeletal stem and progenitor cells (SSPCs) are crucial for bone development, homeostasis and repair. SSPCs are considered to reside in a rather hypoxic niche in the bone, but distinct SSPC niches have been described in different skeletal regions and they likely differ in oxygen and nutrient availability. Currently it remains unknown whether the different SSPC sources have a comparable metabolic profile and respond in a similar manner to hypoxia. In this study, we show that cell proliferation of all SSPCs was increased in hypoxia, suggesting that SSPCs can indeed function in a hypoxic niche in vivo. In addition, low oxygen tension increased glucose consumption and lactate production, but affected pyruvate metabolism cell-specifically. Hypoxia decreased tricarboxylic acid (TCA) cycle anaplerosis and altered glucose entry into the TCA cycle from pyruvate dehydrogenase to pyruvate carboxylase and/or malic enzyme. Finally, a switch from glutamine oxidation to reductive carboxylation was observed in hypoxia, as well as cell-specific adaptations in the metabolism of other amino acids. Collectively, our findings show that SSPCs from different skeletal locations proliferate adequately in hypoxia by rewiring glucose and amino acid metabolism in a cell-specific manner.

Need a simple solution for managing your BibTeX entries? Explore CiteDrive!

  • Web-based, modern reference management
  • Collaborate and share with fellow researchers
  • Integration with Overleaf
  • Comprehensive BibTeX/BibLaTeX support
  • Save articles and websites directly from your browser
  • Search for new articles from a database of tens of millions of references
Try out CiteDrive

More from our Archive